# Bifidobacterium animalis subsp. animalis GY007 Mitigates High Fluoride Exposure-Induced Ileal Injury and Restores the Ileal Microbiota–Metabolome Imbalances

## TL;DR

A probiotic strain, GY007, helps protect the ileum from damage caused by high fluoride exposure by reducing inflammation and restoring gut health.

## Contribution

This study identifies GY007 as a probiotic that mitigates fluoride-induced ileal injury and reveals key metabolites involved in the process.

## Key findings

- GY007 reduced intestinal permeability and oxidative stress in fluoride-exposed mice.
- The probiotic restored ileal mucosal architecture and modulated inflammatory pathways like TLR9/NF-κb/IRF7.
- Microbiome and metabolome analyses showed GY007 reversed microbial and metabolic dysregulation in the ileum.

## Abstract

This study investigated the protective effects of Bifidobacterium animalis subsp. animalis GY007 against ileal injury resulting from fluoride exposure. Three cohorts of experimental mice were examined: a healthy control group (Ctrl), a fluoride exposed group (F), and a group co-treated with both fluoride and the probiotic GY007 (F+Bi). The findings demonstrated that GY007 administration significantly mitigated fluoride-induced ileal injury in mice. This protective effect was evidenced by reduced intestinal permeability, increased expression of tight junction proteins, restoration of ileal mucosal architecture, and decreased oxidative stress levels. In parallel, inflammatory cytokines and markers associated with the TLR9/NF-κb/IRF7 pathway were reduced (TLR9, Myd88, IRAK4, NF-κb, IRF7, TNF-α, IL-6, and IFN-α). Analysis of the microbiome and metabolome demonstrated that GY007 influenced the structure of the ileal microbial community and its associated metabolite profile. Our results suggest that GY007 may play a beneficial role in mitigating fluoride-induced ileal injury and shed light on the alterations in the gut microbial community and metabolome. This study provides new insights into how probiotic repairs the damaged ileum caused by endogenous fluoride exposure through interactions with the host organism.

Exposure to fluoride is strongly associated with impaired intestinal function. Probiotics are widely regarded as an effective strategy to maintain microbial homeostasis and to mitigate the progression of fluoride-induced intestinal injury. This study aimed to evaluate the measurable protective effects of the probiotic strain Bifidobacterium animalis subsp. animalis (B. animalis subsp. animalis) GY007 in reversing high fluoride-induced ileal injury. The results showed that GY007 (1 × 109 CFU/mL, once/daily) attenuated intestinal barrier disruption and alleviated ileal mucosal abnormalities in mice receiving fluoride (24 mg/kg) by gavage for eight consecutive weeks. GY007 attenuated elevated oxidative stress and modulated the inflammatory response associated with the TLR9/NF-κb/IRF7 signaling pathway. Microbiome and metabolomic analyses showed that GY007 reversed the dysregulation of the ileal microbial community structure and metabolite profiles. Spearman’s rank correlation analysis further supported a regulatory role for Bifidobacterium in this protective process and identified three key functional metabolites meriting further investigation: isocytosine (ISO), 7α,24S-dihydroxy-3-oxocholest-4-en-26-oic acid (OIC-7α), and sinapinic acid (SIA). Our findings demonstrate that GY007 protects against fluoride-induced ileal injury and elucidate the associated changes in the intestinal microbial community and metabolite profiles. This study provides new evidence clarifying the restorative effect of the probiotic GY007 on the ileum under environmental fluoride exposure, offering an integrative perspective on the interaction between microorganisms and their host.